Monoclonal antibodies reactive with various human tumor cells have been prepared from murine hybridomas according to standard techniques. Phase I trials of antitumor monoclonal antibodies initiated by the Clinical Investigations Section included studies of anti-T cell monoclonal antibodies in patients with chronic lympohocytic leukemia (CLL) and cutaneous T cell lumphoma (CTCL), anti-melanoma monoclonal antibody in patients with disseminated melanoma, and anti-idiotype monoclonal antibody in patients with malignant lymphoma and CLL. We have treated 13 patients with CLL with the T101 monoclonal antiboyd and have witnessed transient reductions incirculating leukemia cells but have not seen reductions in the size of enlargeed organs or lymph nodes. Of 12 patients with CTCL, five patients had minimal improvement in their skin lesions. Toxicity has included mild fever and minimal shortness of breath. Twenty patients with metastatic melanoma have been treated with an antibody to a 250,000 m.w. melanoma associated antigen. While we have been no reductions in the size of metastatic lesions, we have seen excellent in vivo localization of antibody in cutaneous lesions. We have also successfully imaged patients by radionuclide scans using 111Indium-T101 and 111Indium-9.2.27. We have successfully developed anti-idiotype antibodies for 6 patients with B-cell lymphomas and one with CLL. The patient with CLL was treated with 1.5 grams of anti-idiotype antibody without a clinical response. The other patients have not been treated.